Applying physical science principles to mid-substance Achilles tendinopathy and the relationship to eccentric lengthening exercises.

Mid-substance Achilles tendinopathy is common in the active population. Eccentric (lengthening) exercises are known to be effective in alleviating the clinical condition. To better understand mid-substance Achilles tendinopathy and the response to lengthening exercises physical science principles of elasticity are applied. We apply elastic motion laws to the spring-like tendon as well as the normal and pathological adaptation seen with this common injury. We will validate important assumptions of the spring-like behavior of the tendon and then apply these findings to the injured and rehabilitating states. Our analysis considers that the tendon can be viewed as being spring-like with elasticity principles being applicable and the force exerted on the tendon during lengthening is primarily in a uniaxial direction. This applied lengthening force results in tendon mechanical and structural adaptation. Injury, and ultimately the clinical condition, occurs when the applied force exceeds the ability of the tendon to normally adapt. Morphological changes of the injured tendon are an attempt by the body to make the tendon more compliant. Lengthening exercises can be assessed as achieving this task with an improvement of tendon compliance. Physical science analysis proposes that the preferred rehabilitation tendon pathway is to try and decrease tendon stiffness to allow for more tendon lengthening. The body's morphological alterations of the pathological tendon are also consistent with this approach. For mid-substance Achilles tendinopathy, this adaptation of decreased stiffness ultimately increases the tendons ability to withstand applied force during lengthening.

A multicenter phase II trial of cisplatin and oral etoposide (VP-16) in inoperable non-small-cell lung cancer.

Sixty patients with inoperable non-small-cell lung cancer (NSCLC) were entered into a phase II study that tested the combination of cisplatin (80 mg/m2, day, etoposide intravenously (IV) (100 mg, days 1 and etoposide orally (200 mg/m2, days 3 and 5). The regimen was repeated every 28 days for six courses, after which patients were allowed to receive additional treatment at the discretion of their physician. Overall objective response rate in 51 evaluable patients was 69% (95% confidence interval: range, 56% to 81%), with 16% sustaining complete remission (CR), 53% partial remission (PR), 17% stable disease (SD), and 14% progressive disease (PD). CR was pathologically confirmed by bronchoscopy and biopsy. One patient with a clinical PR underwent surgery and was shown to have a pathologic CR. Median survival of all evaluable patients was 52 weeks, greater than 75 weeks for CR patients, 52 weeks for PR patients, 42 weeks for SD patients, and 13 weeks for PD patients. Eleven patients (21.5%) developed CNS metastases, which resulted in the deaths of ten. Survival was significantly correlated with extent of disease, performance status, and albumin level, but not with histology or weight loss. Tumor response was significantly correlated only with histology (squamous-cell and large-cell undifferentiated carcinoma greater than adenocarcinoma). Side effects were nausea, vomiting, anorexia, alopecia, bone marrow suppression, and nephrotoxicity. One patient died from leukopenia and sepsis. Pharmacokinetic studies in ten patients showed the continuous presence of etoposide in plasma for six days at a level of at least 220 to 480 ng/mL. In order to investigate whether this very effective combination of cisplatin and etoposide can prolong survival in NSCLC, it will be tested as preoperative chemotherapy in a randomized trial in operable patients with T1N1 and T2N0-1 disease.